Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model

Transplantation. 2007 Aug 15;84(3):308-15. doi: 10.1097/


Background: Tissue factor (TF) expression on islets can result in an instant blood-mediated inflammatory reaction (IBMIR) that contributes to early islet loss. We tested whether peritransplant protection of islets from IBMIR with a monoclonal anti-TF antibody (CNTO859) would enhance engraftment in our nonhuman primate marginal mass model.

Methods: Each of six pairs of cynomolgus monkeys (CM) with streptozotocin-induced diabetes was closely matched for metabolic control and was transplanted with 5,000 IEQ/kg allogeneic, ABO-compatible islets from the same donor under the cover of steroid-free immunosuppression. For each pair, experimental animals received islets cultured with 20 microg/mL anti-TF and were dosed with 6 mg/kg anti-TF intravenously, 10-25 min before islet infusion; control monkeys received an equal number of islets from the same preparation cultured without anti-TF and no in vivo treatment.

Results: Early fasting C-peptide (CP) values were different between (P<0.01), but not within, pairs and correlated with in vitro functional capacity of islets as assessed by perifusion (r=0.60; P=0.022). Compared to their matched controls, experimental animals had decreased posttransplant markers of coagulation, higher fasting CP levels (1 month posttransplant and end of study) and prolonged graft function.

Conclusions: These data suggest that pretreatment of islets and the recipient with anti-TF may limit the effects of IBMIR, thereby enhancing islet engraftment and survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Cell Survival / drug effects
  • Diabetes Mellitus, Experimental / surgery
  • Dose-Response Relationship, Drug
  • Fibrinolysis / immunology
  • Graft Survival / immunology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation / immunology*
  • Macaca fascicularis
  • Models, Biological
  • Streptozocin
  • Thromboplastin / drug effects
  • Thromboplastin / physiology*
  • Transplantation Tolerance / immunology*


  • Antibodies, Monoclonal
  • Streptozocin
  • Thromboplastin